Telomere-to-telomere assembly of a complete human X chromosome
Telomere-to-telomere assembly of a complete human X chromosome
复制标题
DOI：
10.1038/s41586-020-2547-7
复制
发表时间：
2020-07-14
期刊：
影响因子：
64.8
通讯作者：
Phillippy, Adam M.
中科院分区：
文献类型：
--
作者：
Miga, Karen H.;Koren, Sergey;Phillippy, Adam M.
经过二十年的改进，目前的人类参考基因组（GRCh 38）是有史以来最准确和完整的脊椎动物基因组。然而，没有一条染色体是首尾相连的，数百个未解决的缺口仍然存在（1，2）。在这里，我们展示了一个人类基因组组装，它超越了GRCh 38（2）的连续性，沿着一个人类染色体的端粒到端粒的无间隙组装。这是通过完整的葡萄胎CHM 13基因组的高覆盖率，超长读取纳米孔测序，结合用于质量改进和验证的互补技术实现的。将我们的努力集中在人类X染色体上（3），我们重建了着丝粒卫星DNA阵列（约3.1 Mb），并关闭了当前参考文献中剩余的29个缺口，包括来自人类假常染色体区域和癌症睾丸扩增子基因家族（CT-X和GAGE）的新序列。这些序列将被整合到未来的人类参考基因组版本中。此外，完整的X染色体与超长纳米孔数据相结合，使我们能够在复杂的串联重复序列和卫星阵列中绘制甲基化模式。我们的研究结果表明，完成整个人类基因组现在是触手可及的，这里提供的数据将促进正在进行的努力，以完成其他人类染色体。高覆盖率，超长读取纳米孔测序用于创建一个新的人类基因组组装，提高了覆盖率和准确性的当前参考（GRCh 38），并包括无间隙，端粒到端粒序列的X染色体。
After two decades of improvements, the current human reference genome (GRCh38) is the most accurate and complete vertebrate genome ever produced. However, no single chromosome has been finished end to end, and hundreds of unresolved gaps persist(1,2). Here we present a human genome assembly that surpasses the continuity of GRCh38(2), along with a gapless, telomere-to-telomere assembly of a human chromosome. This was enabled by high-coverage, ultra-long-read nanopore sequencing of the complete hydatidiform mole CHM13 genome, combined with complementary technologies for quality improvement and validation. Focusing our efforts on the human X chromosome(3), we reconstructed the centromeric satellite DNA array (approximately 3.1 Mb) and closed the 29 remaining gaps in the current reference, including new sequences from the human pseudoautosomal regions and from cancer-testis ampliconic gene families (CT-X and GAGE). These sequences will be integrated into future human reference genome releases. In addition, the complete chromosome X, combined with the ultra-long nanopore data, allowed us to map methylation patterns across complex tandem repeats and satellite arrays. Our results demonstrate that finishing the entire human genome is now within reach, and the data presented here will facilitate ongoing efforts to complete the other human chromosomes.High-coverage, ultra-long-read nanopore sequencing is used to create a new human genome assembly that improves on the coverage and accuracy of the current reference (GRCh38) and includes the gap-free, telomere-to-telomere sequence of the X chromosome.